Abstract: The invention relates to nucleic acids and methods for restoring acid alpha-glucosidase (GAA) activity in patients with Pompe disease using splice-switching technology.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting a xanthine dehydrogenase (XDH) gene, and methods of using such double stranded RNAi agents to inhibit expression of an XDH gene and methods of treating subjects having an XDH-associated disease.

Abstract: Genetically modified microorganisms that have the ability to convert carbon substrates into chemical products such as 2,3-BDO; 1,4-BDO; isobutyraldehyde; isobutanol; 1-butanol; n-butanol; ethanol; fatty alcohols; and fatty acid methyl ester are disclosed. For example, genetically modified methanotrophs that are capable of generating 2,3-BDO; 1,4-BDO; isobutyraldehyde; isobutanol; 1-butanol; n-butanol; ethanol; fatty alcohols; and fatty acid methyl ester at high titers from a methane source are disclosed. Methods of making these genetically modified microorganisms and methods of using them are also disclosed. These microorganisms and methods make use of molecular switches to regulate gene expression.

Abstract: Disclosed are systems and methods that include or utilize composable mammalian elements of transcription (COMET) including engineered recombinant proteins that regulate transcription and engineered DNA promoter sequences that are regulated by the engineered recombinant proteins. The elements may be composed to form logic gates, gene expression cascades and programs, and cell-based biosensors.

Abstract: Dumbbell-shaped DNA minimal vectors represent genetic vectors solely composed of the gene expression cassette of interest and terminal closing loop structures. Dumbbell vectors for small hairpin RNA or microRNA expression are extremely small-sized which is advantageous with regard to cellular delivery and nuclear diffusion. Conventional strategies for the generation of small RNA-expressing dumbbell vectors require cloning of a respective plasmid vector which is subsequently used for dumbbell protection. Here, we present a novel cloning-free method for the generation of small RNA-expressing dumbbell vectors which also does not require any restriction endonucleases. The method comprises the PCR amplification of a universal DNA template using primers containing the sense or antisense strand of the sequence of interest, the denaturing and refolding of the amplified product to form stem-loop structures, and the structures are covalently closed using DNA ligases to obtain dumbbell structures.

Abstract: The present invention relates to recombinant Gram-negative bacterial strains and the use thereof for delivery of heterologous proteins into eukaryotic cells.

Abstract: Described herein are modified MYB46 transcription factors that are more stable and less prone to degradation than corresponding unmodified MYB46 transcription factors. Expression of the modified MYB46 transcription factors within plants improves the structural strength, increases biomass, and enhances fiber strength of the plants.

Abstract: Described herein are plants, plant seeds, and plants cells that are modified to express particular types of cellulose synthase enzymes (but not CesA3, CesA9, or CesA7 enzymes). Such plants, plant seeds and plant cells can be cotton, flax, hemp, jute, sisal, poplar, or eucalyptus plants, plant seeds or plant cells. The modified plants tend to grow taller, have increased cellulose synthesis, have more crystalline cellulose, have wider secondary cell walls, increased biomass, and increased mechanical strength than in a control plant without the expression cassette (e.g., a wild type or parental plant without the expression cassette).

Abstract: The field is related to plant breeding and methods of identifying and selecting plants with resistance to southern corn rust. Provided are methods to identify novel genes that encode proteins providing plant resistance to southern corn rust and uses thereof. These disease resistant genes are useful in the production of resistant plants through breeding, transgenic modification, or genome editing.

Abstract: A lentiviral vector and a method for delivering an exogenous RNA by the lentiviral vector are provided. The lentiviral vector is prepared by transfecting plasmids containing a genome sequence of the lentiviral vector into a virus-producing cell, collecting a supernatant and concentration. Specifically, according to the principle of combining an RNA-binding protein with an RNA sequence identified by the RNA-binding protein, the RNA-binding protein is integrated into a skeleton of a lentivirus GagPol long-chain protein, and the RNA sequence identified by the RNA-binding protein is connected to the exogenous target RNA, so that the exogenous target RNA is packaged into lentiviral particles during the assembly of the lentiviral particles. The exogenous target RNA can be mRNA, gRNA or RNA with other functions. The present invention can be used in the fields of gene editing, gene therapy, cell therapy, immunotherapy, regenerative medicine and basic biology.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

Abstract: Provided for the first time in the present invention is a method for preparing a non-human primate somatic cell cloned animal, which method specifically comprises the steps of: (i) providing a reconstructed egg, wherein the egg comes from the non-human primate (ii) activating the reconstructed egg to form an activated reconstructed egg or activated reconstructed embryo formed by the reconstructed egg; (iii) reprogramming (a) the activated reconstructed egg or (b) embryonic cells of the activated reconstructed embryo to obtain a reprogrammed reconstructed egg or reprogrammed reconstructed embryo; and (iv) regenerating the reprogrammed reconstructed egg or reprogrammed reconstructed embryo to obtain the non-human primate somatic cell cloned animal. The method of the present invention can significantly improve the developmental capacity of nucleus-transplanted embryos in non-human primates (such as monkeys).

Abstract: The present invention provides a carboxylated nanodiamond-mediated CRISPR-Cas9 delivery system for gene editing comprising nanodiamond (ND) particles as the carriers of CRISPR-Cas9 components designed to introduce the mutation in a given gene for repairing a tissue damage.

Abstract: Haploid human embryonic stem cells and cell lines, haploid multipotent human cells, and haploid differentiated human cells are provided. In addition, methods of making and using the haploid human cells are provided.

Abstract: Provided are a storage method and a banking system of cells prepared using somatic cell nuclear transfer (NT) technology with homozygous genotypes of genes of human leukocyte antigen (HLA)-A, HLA-B, HLA-DR, and the like. The banking of NT cell-derived stem cells may be applied to autologous or allogenic patients and can provide transplantable cells and tissue materials for the treatment of various diseases such as diabetes, osteoarthritis, Parkinson's disease, and the like.

Abstract: Provided is a method of inducing the differentiation of a stem cell into nerve progenitor cells, comprising the step (1) of forming homogenous aggregates of stem cells in a serum-free medium (1) and the step (2) of suspension-culturing the homogenous aggregates of stem cells in the presence of a basement membrane reference standard.

Abstract: The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.

Abstract: The present disclosure relates generally to methods of producing rejuvenated T cells, comprising, contacting T cells with at least one reprogramming factor and reactivating the contacted cells; and compositions and methods of using same. The present disclosure also describes cell populations prepared according to methods described herein. The disclosure also provides for methods of treating patients using cell populations prepared by the methods described herein.

Abstract: The present invention provides a method for producing platelets that can improve at least one of the ability of megakaryocyte to produce platelets and the bioactivity of platelets produced even in high-density culture, for example. The method for producing platelets of the present invention includes a platelet producing step of producing platelets from megakaryocytes, wherein the platelet producing step is performed in the presence of at least one of glycine and cysteine.

Abstract: A method of generating multipotent stem cells from adult human peripheral blood cells by isolating the peripheral blood insulin-producing cells and exposing them to adult peripheral blood-derived mitochondria. Adult peripheral blood insulin-producing cells (PB-IPC) are isolated from adult peripheral blood by adherence to a hydrophobic surface with a positive charge, such as a Petri dish. Once the PB-IPC are isolated, mitochondria derived from adult peripheral blood are applied to the isolated PB-IPC. The mitochondria are then taken in by the PB-IPC and enter the nuclei of the PB-IPC, allowing the cells to be reprogrammed, transforming PB-IPC into multipotent stem cells and giving rise to three germ layer-derived cells. Additionally, PB-IPC give rise to functional CD34+ hematopoietic stem cell (HSC)-like cells after treatment with adult peripheral blood-derived mitochondria.

Abstract: A bacteriophage RNA polymerase variant is provided. In some embodiments, the variant may have increased thermostability relative to the corresponding wild type bacteriophage RNA polymerase and/or wild type T7 RNA polymerase. Compositions, kits and methods that employ the variant are also provided.

Abstract: Disclosed are Taq DNA polymerase mutants which exhibit enhanced efficiency in qPCR compared to the wild type Taq DNA polymerase. Such mutants include: V62S, V64S, A70F, F73A, A77F, P253G, E255K, D257R, A259F, A271F, L288S, E289K, S357I, L361S, L376S, P382G, T385I, G418P, R419D, E421K, L461S, A472F, E497K, L498S, E524K, D551R, R556D, S679l, L789S, E189K/E507K/E742K (See Sequence Listing Guide for the mutants' amino acid and protein sequences).

Abstract: The present invention provides a non-naturally occurring composition comprising a CRISPR nuclease comprising a sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 1 or a nucleic acid molecule comprising a sequence encoding the CRISPR nuclease.

Abstract: The present disclosure relates to compositions of matter and methods used to activate effector nucleic acids and effector targets in vivo via a CRISPR-based cascade system. The compositions and methods achieve non-specific delivery of cascade system components to cells yet the cascade system works in a cell-specific manner.

Abstract: The present disclosure relates to variant engineered nucleic acid-guided nucleases that may be used in CRISPR-based cascade assay systems to detect one or more target nucleic acids in a sample. The variant nucleases comprise an activity such that double-stranded DNA substrates do not bind to or are not cleaved by variant LbCas12a nuclease, or bind to or are cleaved very slowly by the variant nuclease, however single-stranded DNA substrates can bind and are cleaved by the variant nuclease, and wherein the variant nuclease exhibits both cis- and trans-cleavage activity.

Abstract: The invention relates to the field of medicine, specifically to the field of treatment of conditions associated with Staphylococcus infection. The invention relates to a novel endolysin polypeptide specifically targeting a bacterial Staphylococcus cell. The invention further relates to said endolysin polypeptide for medical use, preferably for treating an individual suffering from a condition associated with Staphylococcus infection.

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Abstract: Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical compositions containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

Abstract: Embodiments provided herein, provide for polypeptides and molecules comprising a polypeptide having protease activity and a variant Fc molecule, pharmaceutical compositions comprising the same, and methods that can be used to treat disorders, such as IgG mediated disorders.

Abstract: The present disclosure provides, inter alia, a recombinant engineered deubiquitinase (DUB) and methods for treating or ameliorating an inherited ion channelopathy, such as long QT syndrome, Brugada syndrome, or cystic fibrosis, in a subject. Further provided are methods for screening mutations causing such inherited ion channelopathies for a trafficking-deficient mutation that is treatable by the recombinant engineered DUB disclosed herein.

Abstract: The present disclosure provides an O-methyltransferase protein with a highly specific catalytic function for multiple benzylisoquinoline alkaloids (BIAs) parent nuclei and an encoding gene and use thereof. Compared with wild-type O-methyltransferase, the O-methyltransferase protein (SEQ ID NO: 2) shows an enhanced enzymatic activity and a wider substrate scope. The O-methyltransferase protein can catalyze O-methylation of backbones from three BIAs, including monobenzylisoquinolines (norcoclaurine, coclaurine, and N-methylcoclaurine), aporphines (asimilobine and N-methylasimilobine), and protoberberines (scoulerine and tetrahydrocolumbamine). Meanwhile, this O-methyltransferase protein is highly regioselective for each backbone. The O-methyltransferase protein catalyzes methylation of the monobenzylisoquinolines at 6-OH and 7-OH, is only active on 6-OH of the backbone of the aporphines, and mainly catalyzes methylation of the protoberberines at 2-OH.

Abstract: A method for preparing glucosamine includes the steps of converting fructose-6-phosphate (F6P) and an ammonium salt to glucosamine-6-phosphate (GlcN6P) under the catalysis of glucosamine-6-phosphate deaminase (EC 3.5.99.6, GlmD); and producing glucosamine (GlcN) by the dephosphorylation of GlcN6P under the catalysis of an enzyme capable of catalyzing the dephosphorylation. Such a method can be used to prepare glucosamine by in vitro enzymatic biosystem.

Abstract: Provided herein are compositions, methods, devices, and systems for highly accurate and pure RNA synthesis. Also provided herein are nucleic acid libraries comprising RNAs generated by using devices, compositions and methods disclosed herein.

Abstract: A composition for enhancing the production of a homeoprotein includes an inhibitor of lysosomal function. A method for enhancing the production of a homeoprotein, includes treating cells with an inhibitor of lysosomal function, a method for producing an animal cell line continuously expressing a homeoprotein and a method for mass-producing a homeoprotein using the animal cell line.

Abstract: A method and apparatus for screening of cell lines and culture conditions includes a target value setting step that sets a target value relating to a metabolic reaction of a culture cell; a first culturing step; an analysis step; an analysis value calculation step that performs a metabolism analysis based on an analysis result from the analysis step and calculates an analysis value; a culture condition computation step that computes, using a correlation model, a culture condition giving an analysis value most close to the target value, and modifies the culture condition set in the first culturing step to the computed culture condition; a second culturing step that cultures a cell under the modified culture condition; and a screening step.

Abstract: This invention provides a device for screening a candidate substance for an active ingredient to prevent or treat declined kidney function etc. A screening device 1 for screening a candidate substance for an active ingredient to prevent or treat declined kidney function etc. comprises a first measurement value obtaining unit 11 for obtaining a measurement value of a kidney function prediction marker protein and/or a measurement value of mRNA of the protein in a test-substance-treated specimen, and a candidate substance determination unit 14 for determining that the test substance is a candidate substance for the active ingredient based on the measurement value(s) obtained by the first measurement value obtaining unit 11.

Abstract: An identification by mass spectrometry of a microorganism from among reference microorganisms represented by reference data sets includes: determining a set of data of the microorganism according to a spectrum; for each reference microorganism, calculating a distance between the determined and reference sets; and calculating a probability ƒ(m) according to relation f ? ( m ) = pN ? ( m | ? , ? ) pN ? ( m | ? , ? ) + ( 1 - p ) ? N ? ( m | ? _ , ? _ ) where: m is the distance calculated for the reference microorganism; N(m|?,?) is the value, for m, of a random variable modeling the distance between a reference microorganism to be identified and the reference microorganism, when the microorganism is the reference microorganism; N(m|?,?) is the value, for m, of a random variable modeling the distance between a microorganism to be identified and the reference microorganism, when the microorganism is not the reference microorganism; and p is a scalar in the range fr

Abstract: The invention features devices and kits for capturing and culturing microorganisms (e.g., bacteria, fungi, or protists) and methods of using the devices and kits to detect microorganisms in environmental and other samples. The device includes a nutrient media having a flat growth area on which microorganisms can grow. Samples are collected by contacting the device with any environmental sample, e.g., rolling device on a work surface or exposing device to air, or by filtering a sample through a membrane. Microorganisms deposited on the membrane derive nutrients from the underlying media and grow into colonies that can then be detected using methods known in the art. The detected colonies can be imaged digitally or with film.

Abstract: Individuals consuming a prebiotic and who displayed improvements in blood glucose and/or insulin levels also displayed a decrease in the levels of the non-butyrate-producing Firmicutes genus of bacteria Sporacetigenium. Increasing levels of butyrate-producing Firmicutes genera were not consistently correlated with improvements in metabolism in response to prebiotic consumption. In the general population, Sporacetigenium levels are positively correlated with insulin levels.

Abstract: High throughput personal genomic testing has created a need for robust quality control mechanisms to track sample identity, reagent integrity, and other factors with significant influence on assay performance. A method of massively parallel sequencing using an accompanying barcoded molecular standard enables one to track nucleic acid analytes to identify them by project, lot, batch, or patient. The molecular standard contains sequences present in the analyte, allowing it to be processed simultaneously without any other additional reagents. Within the molecular standard, a calibrator sequence permits assessment of fidelity of sequence determination. Additional sequences in the molecular standard may be used to manipulate the molecular standard separate from the analyte. The molecular standard can be used to benchmark sequencing platforms and assess error rates.

Abstract: Compositions and methods are provided including a plurality of analyte detection agents, each analyte detection agent includes a labile tag operatively coupled to the analyte detection agent, each labile tag includes a signal that is different from each other labile tag and each analyte detection agent targeting a different analyte.

Abstract: The present disclosure relates to compositions of matter and assay methods used to detect one or more non-nucleic acid targets of interest in a sample. The compositions and methods provide signal boost upon detection of non-nucleic acid targets of interest in less than one minute and in some instances instantaneously at ambient temperatures down to 25° C. or less, allow for massive multiplexing, high accuracy, minimal non-specific signal generation, and are easily reprogrammable.

Abstract: Compositions and methods for diagnosing and treating asthma and asthma patients a Th2 high asthma phenotype are disclosed.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Abstract: The invention generally relates to assemblies for displacing droplets from a vessel that facilitate the collection and transfer of the droplets while minimizing sample loss. In certain aspects, the assembly includes at least one droplet formation module, in which the module is configured to form droplets surrounded by an immiscible fluid. The assembly also includes at least one chamber including an outlet, in which the chamber is configured to receive droplets and an immiscible fluid, and in which the outlet is configured to receive substantially only droplets. The assembly further includes a channel, configured such that the droplet formation module and the chamber are in fluid communication with each other via the channel. In other aspects, the assembly includes a plurality of hollow members, in which the hollow members are channels and in which the members are configured to interact with a vessel.

Abstract: The present disclose provides methods and systems for amplifying and quantifying nucleic acids and for detecting the presence or absence of a target in a sample. The methods and systems provided herein may utilize a device comprising a plurality of partitions separated from an external environment by a gas-permeable barrier. Certain methods disclosed herein involve subjecting nucleic acid molecules in the plurality of partitions to conditions sufficient to conduct nucleic acid amplification reactions. The nucleic acid molecules may be subjected to controlled heating in the plurality of partitions to generate data indicative of a melting point(s) of the nucleic acid molecules.

Abstract: The present disclosure provides systems and methods for sequencing nucleic acid molecules using tunneling labels. A sequence of a nucleic acid molecule may be identified with high accuracy using a chip comprising sensors, wherein each individual sensor may comprise at least two electrodes separated by a gap. The electrodes may be configured to generate at least one electrical signal upon binding of a tunneling label associated with a nucleotide. Epigenetic information can also be determined at the same time as a nucleic acid sequence.

Abstract: An imaging system includes: a sample container including a flowcell that includes a plurality of attachment elements at a plurality of sample locations, wherein a single DNA template molecule is attached to each of the attachment elements, and further wherein an average distance between adjacent attachment elements is less than Abbe's limit; and an imager positioned to image photo-switching occurring at the plurality of attachment elements by capturing on and off events in a plurality of color channels at the same time as the on and off events are occurring for the attached molecules when a stochastic photo-switching chemistry is applied to all of the attached molecules at the same time causing the attached molecules to fluoresce in the on and off events in up to four different colors.

Abstract: Described herein are variants of alpha-hemolysin having at least one amino acid substitution at H35G, E111N, M113A, and/or K147N in the mature, wild-type alpha-hemolysin amino acid sequence. In certain examples, the variant may have a substitution at E111S, M113S, T145S, K147S, or L135I in the mature alpha-hemolysin amino acid sequence. The ?-hemolysin variants may also include a substitution at H144A and/or a series of glycine residues spanning residues 127 to 131 of the mature, wild-type alpha hemolysin. Also provided are nanopore assemblies including the alpha-hemolysin variants, the assembly having an increased nanopore lifetime. Further, provided are variants that, in addition to providing increased lifetime, provide a decreased time-to-thread. Hence, the variants provided herein both increase nanopore lifetime and improve efficiency and accuracy of DNA sequencing reactions using nanopores comprising the variants.

Abstract: Methods and compositions for making DNA libraries for massive parallel next generation sequencing (NGS), comprises two parts. These methods may be referred to as Triseq sequencing. The first part includes ligating a UMI adapter, amplifying the DNA fragments in the presence of dUTP, enriching the target molecules through primer extension by using a panel of both forward and reverse primers, and removing the dU-containing template DNA. The DNA molecules are organized to primary clones and subclones, labeled by the UMI on 5? and 3? end of the DNA fragments, respectively. The second part includes sequencing the DNA library by NGS, deducing consensus sequence from each subclone, and from within each primary clone, and between the consensus sequences obtained from both forward and reverse primers.